S M Blaney

..To determine the maximum-tolerated dose, dose-limiting toxicity (DLT), and pharmacodynamics of the proteasome inhibitor bortezomib (formerly PS-341) in children with recurrent or refractory solid tumors...

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..A phase I and pharmacokinetic study of IT mafosfamide was performed to determine a dose for subsequent phase II trials...

..A phase I trial of intrathecal (IT) topotecan was performed to determine the optimal dose, the dose-limiting toxic effects, and the incidence and severity of other toxic effects in patients 3 years and older with neoplastic meningitis...

..This article provides an overview of the approaches to the diagnosis, evaluation, and treatment of neoplastic meningitis...

..In conclusion, the recommended Phase II dose of irinotecan administered as a 60-min i.v. infusion daily for 5 days, every 21 days, is 39 mg/m2 in heavily treated and 50 mg/m2 in less-heavily treated children with solid tumors...

..Further detailed pharmacokinetic studies of irinotecan in patients receiving concomitant therapy with enzyme-inducing anticonvulsants are required so that rational dosing recommendations can be provided for this patient population...

..The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetic properties of pemetrexed in children...

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..These and future planned studies of this novel class of cytotoxic agents are critical to defining the ultimate role of topoisomerase I poisons in the treatment of childhood cancer...

..The objectives of this study were to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and anti-tumor effect of irinotecan in pediatric patients with recurrent or refractory malignancies...

..The purpose of this study was to determine the cytotoxic effects of karenitecin and mafosfamide in vitro against leukemia, medulloblastoma, and neuroblastoma cell lines...

..The Pediatric Oncology Group conducted a phase II study to determine the activity of PZA administered as a 3-hour infusion...

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..These xenograft models should facilitate the understanding of medulloblastoma pathogenesis and future preclinical evaluation of new therapies against medulloblastoma...

..We studied the pharmacokinetics and cerebrospinal fluid penetration of clofarabine in a nonhuman primate model...

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..We therefore studied the CSF penetration of nelarabine and ara-G in a nonhuman primate model that has been highly predictive of anticancer drug distribution in humans...

..We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of pemetrexed in a non-human primate model that is highly predictive of human CSF penetration...

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..Secondary objectives included assessment of free and total VPA pharmacokinetics (PKs) and histone acetylation in peripheral blood mononuclear cells (PBMC) at steady state...

..In the Children's Oncology Group (COG) Phase 1 Consortium, pharmacokinetic studies are usually optional. We surveyed the attitudes towards PK studies among subjects in phase 1 trials at COG institutions...

..In conclusion, although ABT-888 potentiation of TMZ was most pronounced in MMR-deficient cells with low MGMT activity, neither MMR proficiency nor MGMT overexpression completely abrogated ABT-888 potentiation of TMZ...

..To evaluate the plasma and cerebrospinal fluid (CSF) pharmacokinetics and CSF penetration of tasidotin and metabolites in a nonhuman primate model...

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..To develop a population pharmacokinetic model of irinotecan and its major metabolites in children with cancer and to identify covariates that predict variability in disposition...

..To determine the tolerability, pharmacokinetics, and mechanisms of temozolomide resistance in children with relapsed or refractory leukemia...

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..A phase II study was performed to determine the efficacy of irinotecan (IRN) in children with refractory solid tumors. Secondary objectives were to evaluate toxicity, pharmacokinetics, pharmacodynamics, and UGT1A1 genotype...

..Future trials should consider strategies to overcome the resistance mechanisms in children with high-grade glioma...

..These data suggest bortezomib could potentiate the cytotoxic effects of combination chemotherapy in patients with leukemia...

..A phase 1 study to determine the maximum-tolerated dose, dose-limiting toxicity, pharmacokinetics, and biological effects of bortezomib in children with recurrent/refractory leukemia...

..We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of NSC 655649 after systemic administration in a nonhuman primate model that is predictive of anticancer drug behavior in humans...

..CONCLUSIONS: There is limited penetration of imatinib into the CSF of nonhuman primates after i.v. and p.o. administration...

..We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of depsipeptide in a nonhuman primate model that is highly predictive of human CSF penetration...

..We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease...

..CONCLUSIONS: The ratio of the CSF AUC to the plasma AUC was less than 5% (range 0.4% to 3.0%), similar to other highly protein-bound topoisomerase inhibitors such as 9-aminocamptothecin and SN-38 (the active metabolite of irinotecan)...

..To evaluate the toxicity, antileukemic activity, and pharmacology of raltitrexed administered weekly for 3 weeks to patients with refractory or recurrent leukemia...

..Recent studies have indicated that thalidomide inhibits angiogenesis. We performed a phase I and pharmacokinetic study of thalidomide with carboplatin in children with refractory solid tumors...

..In an attempt to minimize such stress, the authors describe an enrichment program they designed for use with restrained adult male rhesus macaques...

..In this article, we review the clinical and biologic prognostic factors for classifying medulloblastoma, current strategies for the management of this disease, and potential strategies to prevent or minimize long-term treatment sequelae...

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..Disclosure of potential conflicts of interest is found at the end of this article...

..We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of ABT-888 in a non-human primate (NHP) model that is highly predictive of human CSF penetration...

..Therefore, valproic acid may represent a novel therapeutic option in medulloblastoma treatment...

..The plasma and cerebrospinal fluid (CSF) pharmacokinetics of MP470 were studied in a non-human primate model that is highly predictive of CSF penetration in humans...

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..Immunostaining of myelin basic protein on paraffin sections derived from 18 incompletely resected JPAs suggests that JPA without myelin basic protein-positively stained tumor cells may have a higher tendency to progress...

..Further research is critical to identify new therapeutic strategies for children with or at high risk for leptomeningeal cancer...

..To determine the maximum-tolerated dose, toxicity, pharmacokinetics, and biologic effects of G3139 when administered with doxorubicin and cyclophosphamide to children with relapsed solid tumors...

..Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors...

..To describe the characteristics of pediatric subjects who enroll in phase I trials, to determine the associations between pre-enrollment characteristics and the risk for toxicity, and to analyze response and survival outcomes...

..San Ramon, CA) was conducted in children with neoplastic meningitis following recurrent primary brain tumors to describe toxicities, estimate the maximum tolerated dose (MTD), and document evidence of responses to this agent...

..We conducted a phase I and pharmacokinetic study of the epidermal growth factor receptor (EGFR) inhibitor erlotinib as a single agent and in combination with temozolomide in children with refractory solid tumors...

..However, effective antiemetics and calcium supplementation are necessary with the use of amifostine. Further escalation of irinotecan dosing, using these precautions for amifostine administration, may be possible...

..Radiographic changes following RT make determination of early tumor progression difficult. Metastatic disease is common prior to death...

..Gefitinib did not induce any significant variation in the levels of the assessed parameters, and none of these determinations showed significant predictive or prognostic value...

..We quantified cerebrospinal fluid (CSF) and plasma concentrations of gemcitabine and its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), in nonhuman primates given intrathecal gemcitabine...

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..The goal of these initiatives is to improve the overall outcome for childhood cancer while minimizing the short and long-term sequelae associated with current treatment strategies...

..The MTD of tipifarnib with concurrent radiation is 125 mg/m(2)/dose b.i.d. One-year survival and progression-free survival estimates are 36.4% (SE 16.7%) and 9.4% (SE 6.3%), respectively...

..The recommended phase II dose in children with solid tumors is 17 mg/m2...

..VNP40101M (Cloretazine), a novel DNA alkylating agent, was evaluated in a phase I study in children with recurrent brain tumors...

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..Primary objectives were to estimate the maximum-tolerated dose (MTD) and to describe the dose-limiting toxicities (DLTs) and pharmacokinetics of lonafarnib. Farnesylation inhibition of HDJ-2 in peripheral blood was also measured...

..To determine the recommended phase 2 dose, dose-limiting toxicities (DLT), pharmacokinetic profile, and pharmacodynamics of the heat shock protein (Hsp) 90 inhibitor, 17-allylaminogeldanamycin (17-AAG)...

..Imatinib may increase the risk of ITH, although the incidence of spontaneous hemorrhages in brainstem glioma is sufficiently high that this should be considered in studies of agents in which hemorrhage is a concern...

..Doses of 260 and 340 mg/m(2) provide systemic exposures similar to those of adults who are treated with daily doses of 400 and 600 mg, respectively...

..A phase II study of imatinib in children and young adults with select solid tumors was performed...

..15 mg/kg per day. The response rate in children with relapsed APL is similar to the response rate in adults. This trial was registered as #NCT00020111 at www.ClinicalTrials.gov...

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..Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer...

..The Children's Oncology Group conducted a phase II trial of 21-day continuous infusion topotecan to determine the response rate in pediatric patients with recurrent or refractory malignant solid tumors...

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..It offers leadership in the development of new agents, in new uses of sophisticated radiotherapy, and in the application of new approaches to brain tumor therapy. ..